crossing96/oncoscreening huggingface dataset:
Tumor budding correlates with tumor invasiveness and predicts worse survival in pT1 non-muscle-invasive bladder cancer.	Tumor budding is defined as a single cell or a cluster of up to 5 tumor cells at the invasion front. Due to the difficulty of identifying patients at high risk for pT1 non-muscle-invasive bladder cancer (NMIBC) and the difficulties in T1 substaging, tumor budding was evaluated as a potential alternative and prognostic parameter in these patients. Tumor budding as well as growth pattern, invasion pattern and lamina propria infiltration were retrospectively evaluated in transurethral resection of the bladder (TURB) specimens from 92 patients with stage pT1 NMIBC. The presence of tumor budding correlated with multifocal tumors (p = 0.003), discontinuous invasion pattern (p = 0.039), discohesive growth pattern (p < 0.001) and extensive lamina propria invasion (p < 0.001). In Kaplan-Meier analysis, tumor budding was associated with significantly worse RFS (p = 0.005), PFS (p = 0.017) and CSS (p = 0.002). In patients who received BCG instillation therapy (n = 65), the absence of tumor budding was associated with improved RFS (p = 0.012), PFS (p = 0.011) and CSS (p = 0.022), with none of the patients suffering from progression or dying from the disease. Tumor budding is associated with a more aggressive and invasive stage of pT1 NMIBC and a worse outcome. This easy-to-assess parameter could help stratify patients into BCG therapy or early cystectomy treatment groups.	bladder
Identification of Activated Protein Kinase Cα (PKCα) in the Urine of Orthotopic Bladder Cancer Xenograft Model as a Potential Biomarker for the Diagnosis of Bladder Cancer.	Bladder cancer has a high recurrence rate; therefore, frequent and effective monitoring is essential for disease management. Cystoscopy is considered the gold standard for the diagnosis and continuous monitoring of bladder cancer. However, cystoscopy is invasive and relatively expensive. Thus, there is a need for non-invasive, relatively inexpensive urinary biomarker-based diagnoses of bladder cancer. This study aimed to investigate the presence of activated protein kinase Cα (PKCα) in urine samples and the possibility of PKCα as a urinary biomarker for bladder cancer diagnosis. Activated PKCα was found to be present at higher levels in bladder cancer tissues than in normal bladder tissues. Furthermore, high levels of activated PKCα were observed in urine samples collected from orthotopic xenograft mice carrying human bladder cancer cells compared to urine samples from normal mice. These results suggest that activated PKCα can be used as a urinary biomarker to diagnose bladder cancer. To the best of our knowledge, this is the first report describing the presence of activated PKCα in the urine of orthotopic xenograft mice.	bladder
Unraveling the Photodynamic Activity of Cationic Benzoporphyrin-Based Photosensitizers against Bladder Cancer Cells.	In this study, we report the preparation of new mono-charged benzoporphyrin complexes by reaction of the appropriate neutral benzoporphyrin with (2,2'-bipyridine)dichloroplatinum(II) and of the analogs' derivatives synthesized through alkylation of the neutral scaffold with iodomethane. All derivatives were incorporated into polyvinylpyrrolidone (PVP) micelles. The ability of the resultant formulations to generate reactive oxygen species was evaluated, mainly the singlet oxygen formation. Then, the capability of the PVP formulations to act as photosensitizers against bladder cancer cells was assessed. Some of the studied formulations were the most active photosensitizers causing a decrease in HT-1376 cells' viability. This creates an avenue to further studies related to bladder cancer cells.	bladder
Survival of bladder or renal cancer in patients with CHEK2 mutations.	PURPOSE: The purpose of this study was to compare the clinical characteristics and the survival of CHEK2 mutation positive and CHEK2 mutation negative patients diagnosed with bladder or kidney cancer. MATERIALS AND METHODS: 1016 patients with bladder and 402 cases with kidney cancer and 8302 controls were genotyped for four CHEK2 variants: 1100delC, del5395, IVS2+1G>A and I157T. Predictors of survival were determined among CHEK2 pathogenic variant carriers using the Cox proportional hazards model. The median follow-up was 17.5 years. Covariates included age (≤60; >61 years), sex (female; male), clinical characteristics (stage: TNM, grade, histopathological type), smoking status (non-smoking; smoking) and cancer family history (negative; positive). RESULTS: We found no impact of CHEK2 mutations on bladder or kidney cancer survival. However, we observed a possible increased survival in the subgroup of patients with stage T1 bladder cancer with CHEK2 mutations but this did not meet statistical significance (HR = 0.14; 95% CI 0.02-1.04; p = 0.055). Moreover, we observed that the missense mutations were more frequent in the low grade invasive bladder cancer patient group (OR = 7.9; 95% CI 1.50-42.1; p = 0.04) and in patients with bladder cancer with stage Ta (OR = 2.4; 95% CI 1.30-4.55; p = 0.006). The different results where missense mutations occurs less often we observed among patients with high grade invasive bladder cancer (OR = 0.12; 95% CI 0.02-0.66; p = 0.04) and those with stage T1 disease (OR = 0.2; 95% CI 0.07-0.76; p = 0.01). Our investigations revealed that any mutation in CHEK2 occurs more often among patients with stage Ta bladder cancer (OR = 2.0; 95% CI 1.19-3.47; p = 0.01) and less often in patients with stage T1 disease (OR = 0.31; 95% CI 0.12-0.78; p = 0.01). In the kidney cancer patients, truncating mutations were present more often in the group with clear cell carcinoma GII (OR = 8.0; 95% CI 0.95-67.7; p = 0.05). The 10-year survival for all CHEK2 mutation carriers with bladder cancer was 33% and for non-carriers 11% (p = 0.15). The 10-year survival for CHEK2 mutation carriers with kidney cancer 34% and for non-carriers 20% (p = 0.5). CONCLUSION: CHEK2 mutations were not associated with any change in bladder or kidney cancer survival regardless of their age, sex, smoking status and family history. We observed a potentially protective effect of CHEK2 mutations on survival for patients with stage T1 bladder cancer. CHEK2 missense mutations were more common among patients with low grade invasive bladder cancer and in patients with stage Ta diease. The frequencies of the I157T CHEK2 pathogenic variant were less in patients with high grade invasive bladder cancer and those with stage T1 disease. Among patients with bladder cancer with stage Ta disease, the OR for any mutation in CHEK2 was 2.0 but for those with stage T1 disease, the OR was 0.3. We observed truncating CHEK2 mutations were associated with kidney cancer patients with GII clear cell carcinoma.	bladder
Robotic Female Radical Cystectomy.	Radical cystectomy is the standard of care for patients with nonmetastatic high-risk bladder cancer. Robotic approach to radical cystectomy has been developed to reduce perioperative morbidities and enhance postoperative recovery while maintaining oncologic control. Classically, radical cystectomy in female patient entails anterior pelvic exenteration with removal of the bladder, uterus, fallopian tubes, ovaries, anterior vaginal wall, and urethra. Pelvic organ-sparing radical cystectomy has been adopted in carefully selected patients to optimize postoperative sexual and urinary function, especially in those undergoing orthotopic urinary diversion. In this article, we describe our techniques of both classical and organ-sparing robot-assisted laparoscopic radical cystectomy in female patients. We also review patient selection criteria, perioperative management, and alternative approaches to improve operative outcomes in female patients.	bladder
Patient and public involvement in the design and conduct of a large, pragmatic observational trial to investigate recurrent, high-risk non-muscle-invasive bladder cancer.	BACKGROUND: Patient-centered approaches to research design are particularly important for diseases with complex treatment decision-making, such as recurrent, high-grade non-muscle-invasive bladder cancer (NMIBC). The objective of this article is to describe patient and public involvement (PPI) in designing a large, pragmatic observational trial and to articulate barriers, challenges, and lessons learned for future design. METHODS: Through multistakeholder involvement, a large, pragmatic observational trial was designed to investigate the outcomes of high-risk, recurrent NMIBC, and it was titled Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO). CISTO's design used the Guidance for Reporting Involvement of Patients and the Public 2 reporting checklist for PPI and built on prior engagement infrastructure in partnership with the Bladder Cancer Advocacy Network. RESULTS: CISTO's PPI began with research prioritization to identify the highest priority questions facing patients with NMIBC. A pragmatic observational study design was selected and refined through stakeholder input. PPI included patients and caregivers organized into an advocate advisory board and clinicians, researchers, payers, and industry representatives organized into an external advisory board. An engagement plan was created to define the stages of PPI and the level and nature of the involvement of each group. PPI was measured quantitatively and qualitatively through evaluation surveys and iterative feedback from board members, with changes made for continuous improvement. CONCLUSIONS: Through intentional PPI, CISTO aims to produce pragmatic and generalizable results that will allow patients to make informed decisions for recurrent, high-risk NMIBC based on their personal experiences. LAY SUMMARY: Involving patients and other stakeholders in research ensures that it reflects the outcomes that matter most to them. This is especially important when research focuses on conditions in which patients face difficult decisions about treatment options. This article describes the key role that stakeholders played in shaping the Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO) study. It compares treatments for recurrent noninvasive bladder cancer and describes how stakeholders were engaged to design and develop the study and the practices that supported their involvement.	bladder
"Construction of a survival prediction model for high-and low -grade UTUC after tumor resection based on ""SEER database"": a multicenter study."	BACKGROUND: There are differences in survival between high-and low-grade Upper Tract Urothelial Carcinoma (UTUC). Our study aimed to develop a nomogram to predict overall survival (OS) of patients with high- and low-grade UTUC after tumor resection, and to explore the difference between high- and low-grade patients. METHODS: Patients confirmed to have UTUC between 2004 and 2015 were selected from the Surveillance, Epidemiology and End Results (SEER) database. The UTUCs were identified and classified as high- and low-grade, and 1-, 3- and 5-year nomograms were established. The nomogram was then validated using the Chinese multicenter dataset (patients diagnosed in Shandong, China between January 2010 and October 2020). RESULTS: In the high-grade UTUC patients, nine important factors related to survival after tumor resection were identified to construct nomogram. The C index of training dataset was 0.740 (95% confidence interval [CI]: 0.727-0.754), showing good calibration. The C index of internal validation dataset was 0.729(95% CI:0.707-0.750). On the other hand, Two independent predictors were identified to construct nomogram of low-grade UTUC. The C index was 0.714 (95% CI: 0.671-0.758) for the training set,0.731(95% CI:0.670-0.791) for the internal validation dataset. Encouragingly, the nomogram was clinically useful and had a good discriminative ability to identify patients at high risk. CONCLUSION: We constructed a nomogram and a corresponding risk classification system predicting the OS of patients with an initial diagnosis of high-and low-grade UTUC.	bladder
Prognostic significance of EZH2 and ARID1A expression in urothelial carcinoma: an immunohistochemical study.	Enhancer of zeste homolog 2 (EZH2) and AT-rich interactive domain 1A (ARID1A) expression in urothelial carcinoma (UC) has not been well studied. ARID1A is a novel tumor suppressor gene coding for a chromatin remodeling protein that is mutated in urinary bladder cancer. The enhancer of zeste homolog 2 (EZH2) is a transcriptional repressor involved in gene silencing. Amplification of EZH2 has been reported in several malignancies. This study analyzed the immunohistochemical expression of EZH2 and ARID1A in 56 cases of UC that included (n = 21) cases of radical cystectomy and (n = 35) cases of transurethral resections of bladder tumor (TURBT) with muscle fibers and immunotherapy with adjuvant intravesical bacillus Calmette-Guerin (BCG). The predicting role of both markers for tumor recurrence and recurrence-free survival (RFS) was also analyzed. High EZH2 marker expression was observed in 75% of cases while 78.6% of cases had low ARID1A marker expression. There was a significant negative correlation between the two markers where high EZH2 and low ARID1A expression was significantly associated with higher tumor grade, stage, presence of muscle invasion, lymph node metastasis, presence of concomitant carcinoma in situ (CIS) and higher incidence of recurrence with shorter RFS rate. It was concluded that EZH2 and ARID1A play a role in tumor carcinogenesis and differentiation and could be considered as independent prognostic factors in UC and for use as a potential therapeutic target.	bladder
Prognostic Analysis of Diagnostic Ureteroscopic Biopsy for Intravesical Recurrence of Upper Urinary Tract Urothelial Carcinoma.	OBJECTIVE: The aim of this study was to investigate whether diagnostic ureteroscopy (URS) biopsy is unfavourable for bladder tumour recurrence in upper urinary tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: We performed a retrospective analysis of 195 patients diagnosed with UTUC, who were divided into a diagnostic URS group (URS+) and a nondiagnostic URS group (URS-) according to whether diagnostic ureteroscopic biopsy was performed. A Cox regression model was used to analyse the risk factors for intravesical recurrence (IVR)-free survival (IRFS) and overall survival (OS) in UTUC after radical nephroureterectomy (RNU). Kaplan-Meier analysis was used to estimate the influence of factors on the incidence of IVR and the cumulative survival rate of UTUC. RESULTS: Patients with a maximum tumour diameter of less than 3.1 cm, low-stage tumours, and ureteral tumours were more likely to undergo diagnostic URS before radical surgery. Multivariate Cox regression analysis showed that tumour pathological stage and diagnostic ureteroscopic biopsy can be used as predictors of IVR after RNU (p = 0.019, 0.033). Kaplan-Meier survival analysis found that diagnostic ureteroscopic biopsy was a high-risk factor for IRFS (p = 0.034). Subcomponent analysis showed that pTa/Tis/T1, pT2, pT3/pT4 stage, and diagnostic ureteroscopic biopsy with pTa/Tis/T1 stage were unfavourable for IVR (p = 0.047). CONCLUSION: Diagnostic ureteroscopic biopsy before RNU should be carefully selected for patients with atypical preoperative UTUC. We believe that intravesical chemotherapy drug perfusion can be used after surgery to prevent IVR if biopsy is unavoidable, but this still requires further prospective studies.	bladder
Aberrant FBXW7-mediated ubiquitination and degradation of ZMYND8 enhances tumor progression and stemness in bladder cancer.	ZMYND8, an epigenetic regulator, was identified as a common oncogene across various tumors. However, little was reported about the association between ZMYND8 and bladder cancer. Besides, aberrant mechanisms that contribute to abnormal ZMYND8 expressions still remain unclear. In the current study, we first found that ZMYND8 protein levels were significantly elevated in Bca samples versus normal tissues, but not the mRNA levels. We then utilized the Cell Counting Kit-8 (CCK-8) assay, clone formation assay and transwell analysis to confirm that ZMYND8 could remarkably promote the tumor progression in vitro, including growth capacity and migration. Bioinformatic predictive analysis revealed that E3 ubiquitin ligase FBXW7 interacts directly with ZMYND8 and degrades ZMYND8 in a polyubiquitination manner. Low FBXW7 was a hazard factor for promoting and depending on accumulated ZMYND8 proteins to promote Bca progression. Gene set enrichment analysis (GSEA) further indicated that ZMYND8 was notably associated with stemness process, which was well functionally validated. Lastly, ZMYND8 deficiency was observed to inhibit tumor growth of Bca in vivo, revealing a promising translational significance in Bca treatment. In conclusion, our study for the first time provided evidence for a novel mechanism of FBXW7/ZMYND8 axis in Bca, providing therapeutic vulnerability for individualized cancer treatment.	bladder
Additive effects of resveratrol and doxorubicin on bladder cancer cells.	The treatment of bladder cancer remains a challenge in clinical practice. Different chemotherapeutic protocols can be used; however, it is common to observe tumor recurrence and secondary effects that result in toxicity. Doxorubicin (DOX), one of the most effective anticancer agents used to treat bladder cancer, can cause chronic cardiotoxicity, limiting its use in clinical practice. Resveratrol (RES), a natural product with potential antitumor activity against bladder cancer, is associated with rapid metabolism and low bioavailability and needs to be combined with chemotherapeutic drugs to improve its use. Our study aimed to assess the therapeutic effect of a low concentration of DOX (2 µM) in combination with RES (150, 200 and 250 µM) on two bladder cancer cell lines. We investigated the mechanism of interaction between the drugs by performing cytotoxicity, clonogenic, oxidative stress, cell migration, cell morphology and nuclear division index (NDI) assays. Cytotoxicity evaluation revealed an additive interaction between RES and DOX for both cell lines. Additionally, the results of cell colony formation, oxidative stress, cell migration, cell morphology and NDI assays showed that a combination of DOX and RES was more effective than RES or DOX alone. In conclusion, a low concentration of DOX combined with RES could potentiate the antitumor effects of the drugs on bladder cancer cells, thus overcoming the secondary effects caused by DOX and the low bioavailability of resveratrol.	bladder
A Robust Hypoxia Risk Score Predicts the Clinical Outcomes and Tumor Microenvironment Immune Characters in Bladder Cancer.	BACKGROUND: Bladder cancer (BLCA) is one of the most common urinary malignancies with poor prognosis. There is an unmet need to develop novel robust tools to predict prognosis and treatment efficacy for BLCA. METHODS: The hypoxia-related genes were collected from the Molecular Signatures Database. The TCGA-BLCA cohort was downloaded from the Cancer Genome Atlas and then was randomly divided into training and internal validation sets. Two external validation cohorts were gathered from Gene Expression Omnibus. Also, another independent validation cohort (Xiangya cohort) was collected from our hospital. The Cox regression model with the LASSO algorithm was applied to develop the hypoxia risk score. Then, we correlated the hypoxia risk score with the clinical outcomes, the tumor microenvironment (TME) immune characteristics, and the efficacy prediction for several treatments, which included cancer immunotherapy, chemotherapy, radiotherapy, and targeted therapies. RESULTS: Hypoxia risk score was an independent prognostic factor. A high-risk score indicated an inflamed TME based on the evidence that hypoxia risk score positively correlated with the activities of several cancer immunity cycles and the infiltration levels of many tumor-infiltrating immune cells, such as CD8 + T cells, Dendritic cells, and NK cells. Consistently, the hypoxia risk score was positively related to the expression of several immune checkpoints, such as PD-L1, PD-1, CTLA-4, and LAG-3, as well as the T cell inflamed score. Furthermore, the hypoxia risk score positively correlated with the enrichment scores of most immunotherapy-positive gene signatures. Therefore, patients with higher risk score may be more sensitive to cancer immunotherapy. Meanwhile, the hypoxia risk score was positively related to the sensitivities of several chemotherapeutic drugs, including Cisplatin, Docetaxel, Paclitaxel, Bleomycin, Camptothecin, and Vinblastine. Similarly, the enrichment scores for radiotherapy-predicted pathways and EGFR ligands were higher in the high-risk score group. Conversely, the enrichment scores of several immunosuppressive oncogenic pathways were significantly higher in the low-risk score group, such as the WNT-β-catenin network, PPARG network, and FGFR3 network. CONCLUSIONS: We developed and validated a new hypoxia risk score, which could predict the clinical outcomes and the TME immune characteristics of BLCA. In general, the hypoxia risk score may aid in the precision medicine for BLCA.	bladder
[UPPER TRACT UROTHELIAL CARCINOMA].	Upper tract urothelial carcinoma is a relatively rare malignancy, but with an increasing prevalence. The main risk factor for the disease is smoking. The most common presentation is hematuria or flank pain. Workup is made by imaging of the upper tract - CTU/MRU (Computed Tomography-Urography/Magnetic resonance (MR) urography) and diagnostic uretero-nephroscopy with biopsy. In the past several years there is major advancement in our understanding of the disease and how to treat it, mainly in nephron-sparing treatments. A risk-stratification is usually conducted according to parameters such as tumor size, distribution, and pathologic diagnosis. The low-risk group is usually offered nephron-sparing treatments such as segmental ureterectomy, endoscopic treatments, and lately - local chemotherapy. The high-risk group is usually offered radical resection of the kidney and ureter, with the possible addition of new-adjuvant and adjuvant treatments. In this article we will review the epidemiology, risk factors, diagnosis, and treatment of this malignancy, with a distinction between the risk groups.	bladder